This project emanates from recent collaborative studies by the Principal Investigator which provided immunohistochemical evidence for the presence of several neuropeptides (NP's) within thyroid nerves which innervate both follicle cells and blood vessels. The objectives of the study are to characterize the effects of certain NP's on thyroid hormone secretion and blood flow, and to study the functional relationship between these. These NP's have recently been found to occur in many different tissues and they are often associated with tumors or disease states. However, studies of the functional importance of the NP's have not kept pace with the more descriptive studies of their distribution. This research proposal consists primarily of in vivo experiments in which thyroid hormone secretion and blood flow are determined in the same rats by radiommunoassay and by an adaptation of the radioactive microsphere technique, respectively. The NP's of primary interest are vasoactive-intestinal peptide (VIP), substance P, neuropeptide Y, and peptide HI, but other NP's will also be tested. Test substances are to be administered into a tail vein, carotid artery, or topically applied to one thyroid lobe. All NP's will be tested for interactions with TSH regarding effects on both secretion and blood flow. The possible involvement of endogenous NP's in regulating thyroid secretion and/or blood flow, will be investigated by pharmacological manipulation of endogenous pools, passive immunization, and the use of an animal model with increased VIP innervation of the thyroid. In the case of NP's which affect both secretion and flow, attempts will be made to determine whether either of these effects is a result of the other, rather than being a direct effect of the NP. Most of the in vivo experiments will be performed using anesthetized rats, but some will also be done in unanesthetized animals with chronic vascular catheters. Experiments in hypophysectomized rats will be carried out to determine whether the observed effects of systemic NP infusions are due to direct thyroid effects or secondary to effects on pituitary TSH secretion. Finally, for those NP's found to affect the thyroid in vivo, additional studies will be done using thyroids in vitro.